No abstract

Concurrent ultrasonic tomography and acoustic emission monitoring were employed to study thermally induced microfracturing in an unconfined, 15-cm cube of Lac du Bonnet granite from Atomic Energy of Canada Limited's Underground Research Laboratory. An electrical resistance cartridge heater, placed in a central vertical borehole, was used to cycle the sample to progressively higher peak temperatures between 75øC and 175øC. Tomography data were collected, at room temperature, before and after each thermal cycle. Acoustic emission monitoring proceeded during both heating and cooling phases of each thermal cycle. Microfractures opened above 80øC and eventually coalesced into a macroscopic fracture plane. The macroscopic fracture originated at the outer edges of the sample and then extended inward, parallel to the fast velocity direction, and eventually intersected the borehole. Both acoustic emission locations and slowness difference tomography clearly delineated the fracture plane. We attribute the development of the macroscopic fracture to a thermal gradient cracking mechanism acting upon a brittle, anisotropic medium. 22,231

Ultrasonic tomography and acoustic emission (AE) data were obtained during laboratory hydraulic fracturing tests on two large, unconfined cylinders of Lac du Bonnet grey granite. The cylinders were internally pressurized over four to five cycles prior to final failure. Compressional velocities were measured before and after each pressurization cycle with an array of 16 evenly spaced transducers around the central, cross-sectional plane of each sample. Sixteen channels of whole waveform AE data were recorded during most pressurization cycles and for a period of about 1 hour after final failure in one sample. Compressional velocities were found to be strongly anisotropic, with the in situ vertical direction being the most rapid direction in both samples. The velocity anisotropy is related to the rock's preexisting microcrack fabric. Owing to radial penetration of fluid into the rock, compressional velocities rose over the course of the experiment. A regression analysis showed that the velocity changes can be explained by variations in crack density, inferred from initial velocities, and radial distance from the borehole. Saturation levels consistent with the observed velocity changes were calculated on the basis of the O'Connell and Budiansky theory. Acoustic emissions reoccurred in a few distinct zones over several pressurization cycles. The AE locations allowed two distinct fracture planes to be sharply delineated in one sample. The fracture plane orientations were controlled by the preexisting microcrack fabric in both samples. AE occurred too rapidly during peak pressure failure to permit us to isolate distinct events. Source mechanism analysis of the AE which occurred prior to peak pressure failure in both samples, and during postfailure monitoring in one sample, showed a predominance of double-couple sources. Compressive sources, thought to be related to crushing of asperities during crack closure, and tensile sources, related to mode I crack growth, were also recorded, as well as more complex sources that could not be modeled by the simple source types listed above.(AE) and performed tomographic velocity imaging during these tests to investigate the granite's micromechanical response to the stress field generated by hydraulic fracturing and to investigate fluid penetration effects.Acoustic emissions have been previously used to study hydraulic fracturing in several field studies [e.g., Pearson, 1981;Fehler, 1989] and in a small number of laboratory experiments. Zoback et al. [1977] detected hydrofracture initiation in laboratory samples of gabbro and sandstone by monitoring AE with a single 200-kHz piezoelectric transducer. Lockner and Byerlee [1977] located over 1000 AE events in two samples of Weber sandstone with an array of six piezoelectric transducers. The AE first appeared near the borehole wall in the center of the incipient fracture zone, then spread outward along distinct planes corresponding to the ultimate fracture surfaces, demonstrating that AE hypocenters can be successfully used to determine ...

No abstract

The rare, fatal neurodegenerative disorder Niemann-Pick disease type C1 (NPC1) arises from lysosomal accumulation of unesterified cholesterol and glycosphingolipids. These subcellular pathologies lead to phenotypes of hepatosplenomegaly, neurological degeneration and premature death. The timing and severity of NPC1 clinical presentation is extremely heterogeneous. This study analyzed RNA-Seq data from 42 NPC1 patient-derived, primary fibroblast cell lines to determine transcriptional changes induced by treatment with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a compound currently under investigation in clinical trials. A total of 485 HPβCD-responsive genes were identified. Pathway enrichment analysis of these genes showed significant involvement in cholesterol and lipid biosynthesis. Furthermore, immunohistochemistry of the cerebellum as well as measurements of serum from Npc1m1N null mice treated with HPβCD and adeno-associated virus (AAV) gene therapy suggests that one of the identified genes, GPNMB, may serve as a useful biomarker of treatment response in NPC1 disease. Overall, this large NPC1 patient-derived dataset provides a comprehensive foundation for understanding the genomic response to HPβCD treatment.